Mesenchymal stem cells (MSCs) are multipotent stromal cells originated from bone marrow and other adult tissues. MSCs are capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplantation of bone marrow-derived MSCs has displayed some promise in the management against ischemic injuries such as myocardial infarction. Aging exhibited increased vulnerability of MSCs to hypoxic injury, higher inositol pyrophosphate 7 (IP7) levels, and decreased Akt phosphorylation. Inhibition of inositol hexakis phosphate kinases (IP6Ks) activates Akt signaling, decreases apoptosis, and modulates paracrine profiles in aged MSCs, and this greatly enhances the therapeutic efficacy of aged MSCs in the face of hypoxic injury.